Investigation of the association and flexibility of cationic lipidic peptide dendrons by NMR spectroscopy

Abstract

The cationic peptide dendrons synthesized and studied are lower generation polylysine-based partial dendrimers with or without lipid chains in the core. The dendrons with lipidic chains can be utilized as protein and liposomal mimics because of their unique structural properties. The full assignments of three different dendrons (L)7(NH2)8, (C14)1(L)7(NH2)8 and (C14)3(L)7(NH2)8 were obtained in D2O and H2O/D2O using a 500 MHz NMR spectrometer. The hydrophobic lipidic core of branched polylysine dendrons was found to induce aggregation upon increasing concentration. Because non-lipidic dendrons do not self-assemble, the behaviour and internal structural features of two different dendrons with one and three C14 hydrocarbon chains were explored. The critical association concentration clearly depends on the number of core hydrophobic residues and the association starts at 0.025 mM for (C14)1(L)7(NH2)8 and 0.05 mM for (C14)3(L(7(NH2)8. Chemical shift analysis also revealed that the hydrophobic chains of the dendrons associate in the core, whereas the polar head groups (NH2) are mainly located at the surfaces of the aggregates. The T1 relaxation time measurements showed that the mobility of the hydrocarbon chain is greater with the monomeric form of dendron (C14)1(L)7(NH2)8) than that of monomer (C14)3(L)7(NH2)8. The inter-chain hydrophobic interactions restrict the flexibility of the dendron with three hydrocarbon chains. As expected, the flexibility of the monomeric form is higher than that of the aggregated state for both of the dendrons.

An intrinsically fluorescent dendrimer as a nanoprobe of cell transport

“…The 2D-TOCSY spectrum of the same compound is shown in Figure 3. 1D and 2D 1 H NMR spectroscopy revealed a range of chemical shift values assigned for H -a, Hb, H-g H-d and H -e protons of the dendrimers (Zloh et al 2005). The error in the experimentally determined proton percentages ranged between 0 and (Table I).…”

Cationic Poly-l-lysine Dendrimer Complexes Doxorubicin and Delays Tumor Growth in Vitro and in Vivo

“…The NMR spectra of DOX, DM, and their mixture are shown in Figure 1A and B. A minor downfield chemical shift was observed for CH 2 peaks belonging to γ, δ, and ε methylene groups of the lysine in the DM 15 with chemical shift values of 1.4, 17, and 3.0 ppm, respectively. The change in chemical shift of the methylene groups was about 0.6 Hz, and that might not seem significant.…”

Molecular Modeling to Study Dendrimers for Biomedical Applications

“…Nevertheless, sometimes, specific chemical groups can be used to probe their local environment if they are different enough. As an example, amide protons in a poly( l -glutamic acid) dendrimers had separate NMR chemical shifts and those were used to probe their exposure to solvent in two different generations by changing the temperature [39], as well as to obtain information about flexibility and the association of lipidic peptide G3 dendrons [40].…”